Service of Bone Diseases, Department of Rehabilitation and Geriatrics, University Hospitals of Geneva, Switzerland.
Bone. 2010 Jun;46(6):1574-81. doi: 10.1016/j.bone.2010.02.015. Epub 2010 Feb 21.
Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism.
Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and IGF-I concentrations were measured. Weight was monitored weekly.
bGH caused a dose-dependent increase in plasma IGF-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets.
These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake.
等热量的蛋白质缺乏与骨量减少和骨强度降低有关,同时 IGF-I 水平也会降低。目前尚不清楚生长激素(GH)的给药是否能纠正这些骨代谢的改变。
6 月龄雌性大鼠喂食含有 2.5%或 15%酪蛋白的等热量饮食 2 周。然后,牛生长激素(bGH,0.5 或 2.5mg/kg 体重)或载体通过皮下注射,每天两次,给予两种饮食的大鼠 4 周。在胫骨近端,进行骨密度(BMD)、最大负荷和组织形态计量学分析。此外,还测量了尿脱氧吡啶啉、血浆骨钙素和 IGF-I 浓度。每周监测体重。
bGH 导致无论饮食蛋白含量如何,血浆 IGF-I 呈剂量依赖性增加。然而,bGH 剂量依赖性地降低了低蛋白饮食大鼠的 BMD 和骨强度。在这个短期治疗期间,bGH 对正常蛋白饮食大鼠的 BMD 没有显著影响,但组织形态计量学检测到的骨形成在该组得到改善,而低蛋白组则没有。只有低蛋白 bGH 治疗的动物破骨细胞表面增加。在正常和低蛋白饮食下都可以检测到骨转换标志物的变化。
这些结果强调了饮食蛋白摄入在短期 GH 给药对骨骼反应中的重要性,并强调需要进一步研究 GH 治疗在低蛋白摄入患者中的作用。